Cordain, L., Hickey, M. , Kim K. Malaria and rickets represent selective forces for the convergent evolution of adult lactase persistence. In: Biodiversity in Agriculture: Domestication, Evolution and Sustainability, Gepts P, Famula T, Bettinger R et al. (Eds.), Cambridge University Press, Cambridge, UK, 2011, pp 299-308.
O’Keefe JH, Vogel R, Lavie CJ, Cordain L. Exercise Like a Hunter Gatherer: A Prescription for Organic Physical Fitness. Progress in Cardiovascular Disease, 2011;56:471-479.
Abstract: A large proportion of the health woes beleaguering modern cultures are because of daily physical activity patterns that are profoundly different from those for which we are genetically adapted. The ancestral natural environment in which our current genome was forged via natural selection called for a large amount of daily energy expenditure on a variety of physical movements. Our genes that were selected for in this arduous and demanding natural milieu enabled our ancestors to survive and thrive, leading to a very vigorous lifestyle. This abrupt (by evolutionary time frames) change from a very physically demanding lifestyle in natural outdoor settings to an inactive indoor lifestyle is at the origin of many of the widespread chronic diseases that are endemic in our modern society. The logical answer is to replicate the native human activity pattern to the extent that this is achievable and practical. Recommendations for exercise mode, duration, intensity, and frequency are outlined with a focus on simulating the routine physical activities of our ancient hunter-gatherer ancestors whose genome we still largely share today. In a typical inactive person, this type of daily physical activity will optimize gene expression and help to confer the robust health that was enjoyed by hunter-gatherers in the wild. (Prog Cardiovasc Dis 2011;53:471-479)
Carrera-Bastos P, Fontes Villalba M, O’Keefe JH, Lindeberg S, Cordain L. The western diet and lifestyle and diseases of civilization. Res Rep Clin Cardiol 2011; 2: 215-235.
Abstract: It is increasingly recognized that certain fundamental changes in diet and lifestyle that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have completely adapted. This mismatch between our ancient physiology and the western diet and lifestyle underlies many so-called diseases of civilization, including coronary heart disease, obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteoporosis, which are rare or virtually absent in hunter-gatherers and other non-westernized populations. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial characteristics of the preagricultural environment is an effective strategy to reduce the risk of chronic degenerative diseases.
Cordain L, Friel J. The Paleolithic Athlete: The Original Cross Trainer. In: Anthropology of Sport and Human Movement, Sands R. (Ed.), Lexington Books, 2010, pp. 267-276.
O’Keefe JH, Vogel R, Lavie CJ, Cordain L. Organic Fitness: Physical Activity Patterns Compatible with our Hunter Gatherer Genetic Legacy. Physician and Sports Medicine 2010, 38 (4):11-18.
Abstract: Many of the pervasive health concerns in modern society are the result of diet and lifestyle choices that are at odds with the evolutionary milieu for which we remain genetically adapted. This systematic displacement from a very physically active lifestyle in a natural outdoor environment to a sedentary indoor lifestyle may be at the root of many chronic diseases that are endemic in our culture. A proposed solution is to simulate indigenous human activity patterns in such a way that is possible and practical for individuals to achieve. Suggestions for exercise mode, duration, intensity, and frequency are outlined, with a focus on realigning our daily physical activities with the archetype that is encoded within our genome. In a sedentary individual, this type of daily physical activity should help confer the robust vigorous health that enabled our ancestors to survive and thrive as hunter-gatherers in the wild.
Kuipers RS, Luxwolda MF, Janneke Dijck-Brouwer DA, Eaton SB, Crawford MA, Cordain L, Muskiet FA. Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Brit J Nutr , 2010 Dec;104(11):1666-87.
Abstract: The systematic displacement from a very physically active lifestyle in our natural outdoor environment to a sedentary, indoor lifestyle is at the root of many of the ubiquitous chronic diseases that are endemic in our culture. The intuitive solution is to simulate the indigenous human activity pattern to the extent that this is possible and practically achievable. Suggestions for exercise mode, duration, intensity, and frequency are outlined with a focus on realigning our daily physical activities with the archetype that is encoded within our genome.
Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion. Am J Clin Nutr 2010;91:295-97.
Brand-Miller J, Mann N, Cordain L. Paleolithic nutrition: what did our ancestors eat? In: ISS 2009 Genes to Galaxies. Eds: Selinger A, Green A. The Science Foundation for Physics, University of Sydney. University Publishing Service, University of Sydney, Sydney, 2009; 28-42.
Ramsden CE, Faurot KR, Carrera-Bastos P, Sperling LS, de Lorgeril M, Cordain L. Dietary fat quality and coronary heart disease prevention: a unified theory based on evolutionary, historical, global and modern perspectives. Curr Treat Options Cardiovasc Med; 2009;11:289-301.
Abstract: A large and growing body of evidence indicates that dietary fatty acids regulate crucial metabolic processes involved in the pathogenesis of coronary heart disease (CHD). Despite this evidence, optimal dietary fatty acid intakes for CHD prevention remain unclear. Significant gaps in the modern nutrition literature and contradictions in its interpretation have precluded broad consensus. These shortcomings can be addressed through the incorporation of evolutionary, historical, and global perspectives. The objective of this review is to propose a unified theory of optimal dietary fatty acid intake for CHD prevention that integrates critical insights from evolutionary, historical, global, and modern perspectives. This broad approach may be more likely than previous methods to characterize optimal fatty acid intakes.
Eaton SB, Cordain L, Sparling PB, Cantwell JD. Evolution, body composition and insulin resistance. Preventive Medicine, 2009;49:283-285.
Objective. Better understanding of the relationships between body composition and insulin resistance.
Results. Average human adiposity and sarcopenia have attained unprecedented levels and the resultantly abnormal body composition distorts insulin receptor balance. Compared to evolutionary norms we now have too many adipocyte insulin receptors (in adipose tissue and liver) and too few myocyte insulin receptors. The body’s insulin receptors can be conceptualized as competing for insulin molecules released from the pancreas. When an insulin molecule docks on an adipocyte receptor, substantially fewer glucose molecules are cleared from the blood than when an insulin molecule docks on a myocyte insulin receptor. Populational insulin receptor imbalance would seem to parallel the secular rise in insulin resistance and offers an attractive pathophysiological explanation for the accompanying type 2 diabetes epidemic.
Conclusion. An evolutionary perspective regarding body composition, insulin receptor imbalance, and the consequent impact on carbohydrate metabolism should enhance public acceptance of recommendations to increase physical activity.
Treloar V, Logan AC, Danby FW, Cordain L, Mann NJ. Comment on acne and glycemic index. J Am Acad Dermatol. 2008 Jan;58(1):175-7.
Eaton SB, Cordain L, Sebastian A. The Ancestral Biomedical Environment In: Endothelial Biomedicine. W.C. Aird (Ed), Cambridge University Press, 2007, pp. 129-134.
Cordain L, Gotshall RW, Eaton SB, Eaton SB III. Actividad fisica, gasto energetico y forma fisica: una perspective evolucionista. IRREC 2007;3: 3-9. Spanish language translation of: Cordain L, Gotshall RW, Eaton SB, Eaton SB III. Physical activity, energy expenditure and fitness: an evolutionary perspective. Int J Sports Med 1998; 19:328-335.
Cordain L. Implications of Plio-Pleistocene Hominin Diets for Modern Humans. In: Early Hominin Diets: The Known, the Unknown, and the Unknowable. Ungar, P (Ed.), Oxford University Press, Oxford, 2006, 363-83.
Cordain L. Saturated fat consumption in ancestral human diets: implications for contemporary intakes. In: Phytochemicals, Nutrient-Gene Interactions, Meskin MS, Bidlack WR, Randolph RK (Eds.), CRC Press (Taylor & Francis Group), 2006, pp. 115-126.
Cordain L., Hickey MS. Ultraviolet radiation represents an evolutionary selective pressure for the south-to-north gradient of the MTHFR 677TT genotype. Am J Clin Nutr 2006;84:1243.
O’Keefe JH Jr, Cordain L, Jones PG, Abuissa H. Coronary artery disease prognosis and C-reactive protein levels improve in proportion to percent lowering of low-density lipoprotein. Am J Cardiol. 2006 Jul 1;98(1):135-9.
Abstract: This editorial outlines the data supporting aggressive lipid goals and options for treating low-density lipoprotein (LDL) cholesterol to a range of approximately 30 to 70 mg/dl. The physiologically normal cholesterol range is approximately 30 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and virtually all wild mammals. Randomized statin trials in patients with recent acute coronary syndromes and stable coronary artery disease have demonstrated that cardiovascular events are reduced and cardiovascular survival optimized when LDL cholesterol is reduced to low-density lipoprotein. Am J Cardiol. 2006 Jul 1;98(1):135-9.
O’Keefe J, Cordain L, Harris WH, Moe RM, Vogel R. Response to letter to the editor: RE: The optimal low-density lipoprotein is 50 to 70 mg/dl. J Am Coll Cardiol 2005;45:1732.
Abuissa H, O’Keefe JH, Cordain, L. Realigning our 21st century diet and lifestyle with our hunter-gatherer genetic identity. Directions Psych 2005;25: SR1-SR10.
Abstract: Within the dermatology community, a general consensus has emerged that diet is unrelated to the etiology of acne. Except for two poorly designed studies, now more than 30 years old, there are few objective data to support this notion. In contrast, a large body of evidence now exists showing how diet may directly or indirectly influence the following five proximate causes of acne: (1) increased proliferation of basal keratinocytes within the pilosebaceous duct; (2) incomplete separation of ductal corneocytes from one another via impairment of apoptosis and subsequent obstruction of the pilosebaceous duct; (3) androgen-mediated increases in sebum production; (4) colonization of the comedo by Propionibacterium acnes; and (5) inflammation both within and adjacent to the comedo. This article will provide a review of the currently available literature on the association between diet and acne vulgaris as well as a discussion of the physiologic principles that may underlie this association.
Hoyt G, Hickey MS, Cordain L. Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk. Br J Nutr 2005;93:175-177.
Abstract: In most carbohydrate-containing foods, the blood insulin response is predictable and is closely linked to the food’s glycaemic index (GI). A single study, examining whole milk and fermented milk products made from whole milk, recently reported a large dissociation between the GI and insulinaemic index (II) in healthy normal adults. Because the fat component of a food may influence the GI and II, it is unclear if a similar dissociation may exist for skimmed milk in normal adults. We determined the GI and II of both skimmed and whole milk in nine healthy, male (n 6) and female (n 3) subjects (23·6 (SD 1·4) years). No significant (P.0·05) differences existed between GI and II for skimmed and whole milks. Significant (P,0·05) differences were observed between the actual and predicted areas under the insulin curves for both skimmed milk (predicted 1405 (SD 289) pmol £ min/l; actual 6152 (SD 1177) pmol £ min/l) and whole milk (predicted 1564 (SD 339) pmol £ min/l; actual 5939 (SD 1095) pmol £ min/l). Consequently, a large and similar dissociation of the GI and II existed for both whole milk (42 (SD 5) and 148 (SD 14)) and skimmed milk (37 (SD 9) and 140 (SD 13)). It is concluded that the dissociation of the GI and II in milk is not related to its fat content.
Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the western diet: Health implications for the 21st century. Am J Clin Nutr 2005;81:341-54.
Abstract: There is growing awareness that the profound changes in the environment (e.g., in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry 10,000 years ago occurred too recently on an evolutionary time scale for the human genome to adjust. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns of contemporary Western populations, many of the so-called diseases of civilization have emerged. In particular, food staples and food-processing procedures introduced during the Neolithic and Industrial Periods have fundamentally altered seven crucial nutritional characteristics of ancestral hominin diets: 1) glycemic load; 2) fatty acid composition; 3) macronutrient composition; 4) micronutrient density; 5) acid-base balance; 6) sodium-potassium ratio; and 7) fiber content. The evolutionary collision of our ancient genome with the nutritional qualities of recently introduced foods may underlie many of the chronic diseases of Western civilization.
O’Keefe J, Cordain L, Harris WH, Moe RM, Vogel R. Response to letter to the editor: RE: Optimal lipids, statins, and dementia. J Am Coll Cardiol 2005;45:964-65.
O’Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004 Jun 2;43(11):2142-6.
Abstract: The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.
Lindeberg S, Ahren B, Cordain L, Rastam L. Serum uric acid in traditional Pacific Islanders and in Sweden. J Intern Med 2004; 255:373-378.
Background. In some western populations, increased serum uric acid has been positively associated with cardiovascular disease, possibly because hyperuricaemia could be an untoward part of the insulin-resistant metabolic syndrome. However, there is evidence that uric acid is a free radical scavenger capable of inhibiting LDL oxidation. Amongst the traditional horticulturalists of Kitava, Trobriand Islands, Papua New Guinea, cardiovascular disease, hypertension, hyperinsulinaemia and abdominal obesity are absent or rare. In contrast, serum triglycerides are similar to Swedish levels.
Objective. To compare serum uric acid between nonwesternized and westernized populations.
Methods. Fasting levels of serum uric acid were measured cross-sectionally in 171 Kitavans aged 20–86 years and in 244 randomly selected Swedish subjects aged 20–80 years.
Results. There were small differences in serum uric acid between the two populations, although a slight increase with age was found only in Swedish males (r 1= 0.20; P 1= 0.03) and females (r 1= 0.36; P < 0.0001). Above 40 years of age, uric acid was approximately 10 % lower in Kitavans, a difference which was statistically significant only in males, possibly because of the limited number of females. Regarding hyperuricaemia, two Kitavan males had uric acid above 450 lmol L)1 whilst none of the females was above 340 lmol L)1. Amongst the Swedish subjects, five of 117 males and 19 of 127 females had hyperuricaemia according to these definitions.
Conclusion. The rather similar uric acid levels between Kitava and Sweden imply that uric acid is of minor importance to explain the apparent absence of cardiovascular disease in Kitava.
Keywords: diet, epidemiology, humans, insulin resistance, Papua New Guinea, uric acid.
Cordain L, O’Keefe J.H. Reply: The hunter-gatherer diet. Mayo Clin Proc 2004; 79:703-04.
O’Keefe J.H., Cordain L. Cardiovascular disease as a result of a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st century hunter-gatherer. Mayo Clin Proc 2004;79:101-108.
Abstract: Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [ω-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter gatherer genetic legacy and suggests practical steps to realign our modern milieu with our ancient genome in an effort to improve cardiovascular health.
Lindeberg S, Cordain L, Eaton B. Biological and clinical potential of a Palaeolithic diet. J Nutr Environ Med 2003;13:149-160.
Abstract: To explore the possibility that a Palaeolithic diet, i.e., one that corresponds to what was available in any of the ecological niches of pre-agricultural humans (1.5 million-10,000 years BP), is optimal in the prevention of age-related degenerative disease.
Design: Literature review.
Materials and Methods: Between 1985 and December 2002, more than 200 scientific journals in medicine, nutrition, biology and anthropology were systematically screened for relevant papers. Computer-based searches and studies of reference lists in journals and books provided a vast number of additional papers.
Results: Increasing evidence suggests that a Palaeolithic diet based on lean meat, fish, vegetables and fruit may be effective in the prevention and treatment of common Western diseases. Avoiding dairy products, margarine, oils, refined sugar and cereals, which provide 70 % or more of the dietary intake in northern European populations, may be advisable. Atherosclerosis is highly dependent on dietary manipulation in animal experiments. Atherogenic dietary factors include fat (any type) and casein, and hypothetically cereals. Stroke, ischaemic heart disease and type 2 diabetes seem largely preventable by way of dietary changes in a Palaeolithic direction. And insulin resistance, which may have far-reaching clinical implications as a cause of unregulated tissue growth, may also respond to an ancestral diet.
Conclusions: Lean meat, fish, vegetables and fruit may be optimal, rather than a strictly vegetarian diet, in the prevention of cardiovascular disease, diabetes and insulin resistance.
Keywords: Palaeolithic diet, evolutionary medicine, nutrition, health promotion, cardiovascular disease, metabolic syndrome.
Cordain L, Response to omega-3 fatty acids and acne. Arch Dermatol 2003;139:942-3.
Lindeberg S, Ahren B, Cordain L, Nilsson-Ehle P, Vessby B, Nilsson A. Determinants of serum triglycerides and high-density lipoprotein cholesterol in traditional Trobriand Islanders – the Kitava Study. Scand J Clin Lab Invest 2003;63:175-180.
Abstract: To analyse variables explaining the variation between serum triglycerides (TGs) and high density lipoprotein cholesterol (HDL-C) in a non-western population characterized by unfavourable TG and HDL-C levels despite marked leanness, low blood pressure and low fasting serum insulin. The study subjects included traditional Pacific Islanders from Kitava, Trobriand Islands, Papua New Guinea and a population in Sweden.
Methods: The study was designed as a cross-sectional survey. Fasting serum lipoproteins and apolipoproteins, insulin, blood pressure and anthropometric measurements were analysed in 122 male and 47 female Kitavans aged 20 – 86 years and in a control population of 729 healthy men and women aged 20 – 66 from Uppsala. Main outcome measures were determinants of TG and HDL-C using a simple and multiple linear regression analysis.
Results: A negative association was found between TGs and HDL-C in Kitava (r~20.38, pv0.0001) and Sweden (r~20.46, pv0.0001), while TGs were positively associated with non-HDL-C and ApoB in both groups. In contrast to what was found in the Swedish subjects, TG and HDL-C levels were not associated with body mass index, waist circumference, glucose, insulin or systolic blood pressure in the Kitavans.
Conclusion: Despite an apparent absence of cardiovascular disease and the metabolic syndrome in the Kitavans, the relationship between TGs and HDL-C was similar to that observed in Caucasians, while neither of the variables was associated with markers of insulin sensitivity in the Kitavans. Whether the findings can be explained by normal physiology or partially reflect the high intake of carbohydrates and saturated fat in Kitava is uncertain.
Abstract: Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor a, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body’s endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J. Acne vulgaris: a disease of Western civilization. Arch Dermatol. 2002 Dec;138(12):1584-90.
BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in non-westernized societies. Herein we report the prevalence of acne in 2 non-westernized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in non-westernized environments may influence the development of acne.
OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed.
CONCLUSIONS: The astonishing difference in acne incidence rates between non-westernized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.
Eaton SB, Eaton SB III, Cordain L. Evolution, diet and health. In: Ungar PS, Teaford MF (Eds.), Human Diet: Its Origins and Evolution. Mawah, New Jersey, Greenwood Publishers, 2002, pp. 7-17.
BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95 % of the adolescent population. In men and women older than 25 years, 40 % to 54 % have some degree of facial acne, and clinical facial acne persists into middle age in 12 % of women and 3 % of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in two nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne.
OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed.
CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.
Cordain L, The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. J Am Neutraceut Assoc 2002; 5:15-24.
Cordain L, Eaton SB, Brand Miller J, Lindeberg S, Jensen C. An evolutionary analysis of the etiology and pathogenesis of juvenile-onset myopia. Acta Opthalmolgica, 2002,80:125-135.
Abstract: The available evidence suggests that both genes and environment play a crucial role in the development of juvenile-onset myopia. When the human visual system is examined from an evolutionary perspective, it becomes apparent that humans, living in the original environmental niche for which our species is genetically adapted (as hunter-gatherers), are either slightly hypermetropic or emmetropic and rarely develop myopia. Myopia occurs when novel environmental conditions associated with modern civilization are introduced into the hunter-gatherer lifestyle. The excessive near work of reading is most frequently cited as the main environmental stressor underlying the development of myopia. In this review we point out how a previously unrecognized diet-related malady (chronic hyperinsulinaemia) may play a key role in the pathogenesis of juvenile-onset myopia because of its interaction with hormonal regulation of vitreal chamber growth.
Cordain L, Eaton SB, Brand Miller J, Mann N, Hill K. The paradoxical nature of hunter-gatherer diets: Meat based, yet non-atherogenic. Eur J Clin Nutr 2002;56 (suppl 1):S42-S52.
Objective: Field studies of twentieth century hunter-gathers (HG) showed them to be generally free of the signs and symptoms of cardiovascular disease (CVD). Consequently, the characterization of HG diets may have important implications in designing therapeutic diets that reduce the risk for CVD in Westernized societies. Based upon limited ethnographic data (n = 58 HG societies) and a single quantitative dietary study, it has been commonly inferred that gathered plant foods provided the dominant energy source in HG diets.
Method and Results: In this review we have analyzed the 13 known quantitative dietary studies of HG and demonstrate that animal food actually provided the dominant (65 %) energy source, while gathered plant foods comprised the remainder (35 %). This data is consistent with a more recent, comprehensive review of the entire ethnographic data (n = 229 HG societies) that showed the mean subsistence dependence upon gathered plant foods was 32 %, whereas it was 68 % for animal foods. Other evidence, including isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid gut size, low activity levels of certain enzymes, and optimal foraging data all point toward a long history of meat-based diets in our species. Because increasing meat consumption in Western diets is frequently associated with increased risk for CVD mortality, it is seemingly paradoxical that HG societies, who consume the majority of their energy from animal food, have been shown to be relatively free of the signs and symptoms of CVD.
Conclusion: The high reliance upon animal-based foods would not have necessarily elicited unfavorable blood lipid profiles because of the hypolipidemic effects of high dietary protein (19-35 % energy) and the relatively low level of dietary carbohydrate (22-40 % energy). Although fat intake (28-58 % energy) would have been similar to or higher than that found in Western diets, it is likely that important qualitative differences in fat intake, including relatively high levels of MUFA and PUFA and a lower ω-6/ω-3 fatty acid ratio, would have served to inhibit the development of CVD. Other dietary characteristics including high intakes of antioxidants, fiber, vitamins and phytochemicals along with a low salt intake may have operated synergistically with lifestyle characteristics (more exercise, less stress and no smoking) to further deter the development of CVD.
Cordain L, Watkins BA, Florant GL, Kehler M, Rogers L, Li Y. Fatty acid analysis of wild ruminant tissues: Evolutionary implications for reducing diet-related chronic disease. Eur J Clin Nutr, 2002;56:181-191.
Hypotheses: Consumption of wild ruminant fat represented the primary lipid source for pre-agricultural humans. Hence, the lipid composition of these animals’ tissues may provide insight into dietary requirements that offer protection from chronic disease in modern humans.
Method: We examined the lipid composition of muscle, brain, marrow and subcutaneous adipose tissue (AT) from 17 elk (Cervus elaphus), 15 mule deer (Odocoileus hemionus), and 17 antelope (Antilicapra americana) and contrasted them to wild African ruminants and pasture and grain-fed cattle.
Results: Muscle fatty acid (FA) was similar among North American species with polyunsaturated fatty acids=saturated fatty acids (P=S) values from 0.80 to 1.09 and n-6=n-3 FA from 2.32 to 2.60. Marrow FA was similar among North American species with high levels (59.3-67.0 %) of monounsaturated FA; a low P=S (0.24 – 0.33), and an n-6=n-3 of 2.24 – 2.88. Brain had the lowest n-6=n-3 (1.20 – 1.29), the highest concentration of 22:6 n-3 (elk, 8.90 %; deer, 9.62 %; antelope, 9.25 %) and a P=S of 0.69. AT had the lowest P=S (0.05 – 0.09) and n-6=n-3 (2.25 – 2.96). Conjugated linoleic acid (CLA) isomers were found in marrow of antelope (1.5 %), elk (1.0 %) and deer (1.0 %), in AT (deer, 0.3 %; antelope, 0.3 %) in muscle (antelope, 0.4 %; elk, trace), but not in brain.
Conclusions: Literature comparisons showed tissue lipids of North American and African ruminants were similar to pasture-fed cattle, but dissimilar to grain-fed cattle. The lipid composition of wild ruminant tissues may serve as a model for dietary lipid recommendations in treating and preventing chronic disease.
Eaton SB, Cordain L. Evolutionary Health Promotion. A consideration of common counter-arguments. Prev Med 2002;34:119-123.
Abstract: The proposal that Late Paleolithic (50,000-10,000 BP) ancestral experience might serve as a model for prevention research and even, if justified by experiment, as a paradigm for health promotion recommendations is sometimes discounted, before critical assessment, because of reservations based on unjustified preconceptions. Most often such biases involve comparative life expectancy, potential genetic change since agriculture, the heterogeneity of ancestral environments, and/or innate human adaptability. This paper examines these topics and attempts to show that none of them justifies a priori dismissal of the evolutionary approach to preventive medicine. Evolutionary health promotion may ultimately be invalidated because of its falsification by experiment or because another theory accords better with known facts, but these commonly held prejudices should not forestall its thoughtful consideration and investigative evaluation.
Eaton SB, Strassman BI, Nesse RM, Neel JV, Ewald PW, Williams GC, Weder AB, Eaton SB 3rd, Lindeberg S, Konner MJ, Mysterud I, Cordain L. Evolutionary health promotion. Prev Med 2002;34:109-118.
Abstract: Health promotion’s promise is enormous, but its potential is, as yet, unmatched by accomplishment. Life expectancy increases track more closely with economic prosperity and sanitary engineering than with strictly medical advances. Notable achievements in the past century – the decreased incidences of epidemic infections, dental caries, and stomach cancer – are owed to virologists, dentists, and (probably) refrigeration more than to physicians. Prevention speaks against tobacco abuse with a single voice, but in many other areas contradictory research findings have generated skepticism and even indifference among the general public for whom recommendations are targeted. Health promotion’s shortcomings may reflect lack of an overall conceptual framework, a deficiency that might be corrected by adopting evolutionary premises: (1) The human genome was selected in past environments far different from those of the present. (2) Cultural evolution now proceeds too rapidly for genetic accommodation – resulting in dissociation between our genes and our lives. (3) This mismatch between biology and lifestyle fosters development of degenerative diseases. These principles could inform a research agenda and, ultimately, public policy: (1) Better characterize differences between ancient and modern life patterns. (2) Identify which of these affect the development of disease. (3) Integrate epidemiological, mechanistic, and genetic data with evolutionary principles to create an overarching formulation upon which to base persuasive, consistent, and effective recommendations.
Mickleborough TD, Gotshall RW, Kluka E, Miller CW, Cordain L. Dietary chloride as a possible determinant of the severity of exercise-induced asthma. Eur J Appl Physiol 2001;85:450-56.
Abstract: Dietary sodium chloride (NaCl) has been shown to alter the severity of exercise-induced asthma, but it is not known if the sodium and chloride ions have independent effects in this regard. The hypothesis tested in the present study was that both a low sodium, low chloride diet and a high sodium, low chloride diet would improve post-exercise pulmonary function in subjects with exercise-induced asthma (EIA) compared to a normal NaCl diet (NSD); but that neither of these diets would have an effect on post-exercise pulmonary function in control (non-EIA) subjects. Eight subjects who suffered from EIA and eight subjects who did not (control) took part in a double-blind crossover study. Pre- and post-exercise pulmonary function was assessed after 2 weeks on a NSD, a low NaCl diet (LSD, low sodium, low chloride) or a sodium bicarbonate diet (NaHCO3 diet, high sodium, low chloride). A 1 week washout period occurred between diets. Altering dietary sodium or chloride had no effect on pre-exercise (baseline) pulmonary function in either group or on post-exercise pulmonary function in control subjects. However, both the LSD and the NaHCO3 diet lessened the deterioration in post-exercise pulmonary function in EIA subjects. Comparing results from pre- to post-exercise, forced expiratory volume in 1 s (FEV1) at 15 min post-exercise differed significantly (P<0.05) between diets [mean (SEM) 7 (4)% on the LSD, 14 (4)% on the NaHCO3 diet, and 19 (2)% on the NSD]. Similar patterns were observed for forced vital capacity (FVC), forced expiratory flow rate at 25%–75% FVC and peak expiratory flow rate. The NaHCO3 diet lessened the deterioration of post-exercise pulmonary function, but not to the extent of LSD. These data suggest that both sodium and chloride contribute to the worsening of EIA symptoms seen after consuming a normal or high NaCl diet.
Mickleborough TD, Gotshall RW, Rhodes J, Tucker A, Cordain L. Elevating dietary salt exacerbates leukotrienes-dependent hyperpnea-induced airway obstruction in guinea pigs. J Appl Physiol 2001, 91:1061-66.
Abstract: Previous studies have indicated that increased dietary salt consumption worsens postexercise pulmonary function in humans with exercise-induced asthma (EIA). It has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of EIA) are mediated by similar mechanisms. Therefore, the purpose of this study was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential pathway of action of dietary salt was investigated by blocking leukotriene (LT) production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs were split into two groups. One group (n = 16) of animals ingested a normal-salt diet (NSD) for 2 wk; the other group (n = 16) ingested a high-salt diet (HSD) for 2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered either saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed for electrolyte concentrations and urinary LTE(4). The HSD elicited higher airway inspiratory pressures (Ptr) than the NSD (P < 0.001) postchallenge. However, after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was blocked in both diet groups (P < 0.001). Nonetheless, the HSD group continued to demonstrate slightly higher Ptr than the NSD group (P < 0.05). Urinary LTE(4) excretion significantly increased in the HSD group compared with the NSD group within treatment groups. This study has demonstrated that dietary salt loading exacerbated the development of HIAO in guinea pigs and that LT release was involved in HIAO and may be moderated by changes in dietary salt loading.
Eaton SB, Cordain L, Eaton SB. An evolutionary foundation for health promotion. World Rev Nutr Diet 2001; 90: 5-12.
Cordain L, Watkins BA, Mann NJ. Fatty acid composition and energy density of foods available to African hominids: evolutionary implications for human brain development. World Review of Nutrition and Dietetics, 2001, 90:144-161.
Cordain L. Syndrome X: Just the tip of the hyperinsulinemia iceberg. Medikament 2001;6:46-51.
Abstract: When body tissues become resistant to insulin the pancreas is frequently able to
maintain normal glucose tolerance by sustaining a relative degree of compensatory
hyperinsulinemia. The onset of impaired glucose tolerance or type 2 diabetes marks a
failure of the pancreas to maintain this state of compensatory hyperinsulinemia.
Compensatory hyperinsulinemia is not necessarily benign and underlies several of the
most common and deadly chronic diseases in western, industrialized nations.
Hypertension, abnormal glucose tolerance, type 2 diabetes, dyslipidemia [increased
plasma triacylglycerol, decreased high density lipoproteins, and smaller, denser low
density lipoproteins] , coronary artery disease (CAD), and obesity, are all linked to
insulin resistance and have been collectively termed syndrome X (1,2). Abnormalities of
fibrinolysis and hyperuricaemia also appear to be members of the cluster of maladies
comprising syndrome X (2). Because insulin resistance is such a common phenomenon
(afflicting at least 25 %) of the population, it has been suggested that the various facets of
syndrome X are involved to a substantial degree in the cause and clinical course of the
major diseases of Western civilization (2). In the past 2 years emerging evidence suggests that the web of diseases and abnormalities associated with insulin resistance may extend far beyond the common
maladies (obesity, type 2 diabetes, hypertension, dyslipidemia and CAD) that frequently
present themselves concurrently in patients. Such diverse abnormalities and illnesses as
polycystic ovary syndrome (PCOS), acne, myopia, epithelial cell cancers (breast,
prostate and colon), reduced age of menarche and the secular trend for increased stature are all linked to the compensatory hyperinsulinemia of insulin resistance by hormonal
Cordain, L., Brand Miller, J., Eaton, S.B. & Mann, N. (2001). Reply to ARP Walker (letter). American Journal of Clinical Nutrition,73: 354-355.
Abstract: We appreciated and enjoyed Walker’s constructive comments and interesting insights and agree with many, but not all, of his conclusions. Numerous epidemiologic data support the notion that increasing Westernization and industrialization in human populations is associated with a greater incidence of chronic degenerative diseases. It is almost axiomatic that changes in diet and activity levels initiated by Westernization and industrialization are largely responsible for these health disorders. As human societies stray farther and farther from the original environmental conditions (both diet and exercise) for which our present genome was selected, it is not unexpected that ill-health effects should emerge
Cordain, L., Brand Miller, J., Eaton, S.B. & Mann, N. (2000). Macronutrient estimations in hunter-gatherer diets (letter). American Journal of Clinical Nutrition,72: 1589-90.
Abstract: Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45–65% of energy) of animal food. Most (73%) of the worldwide hunter-gatherer societies derived >50% (≥56–65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (≥56–65% of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19–35% of energy) at the expense of carbohydrates (22–40% of energy).
Cordain, L., Brand Miller, J., Eaton, S.B. & Mann, N. (2000). Hunter-gatherer diets – a shore based perspective (letter). American Journal of Clinical Nutrition,72: 1585-86.
Gotshall RW, Mickleborough TD, Cordain L. Dietary salt restriction alters pulmonary function in exercise-induced asthmatics. Medicine and Science in Sports and Exercise, 2000;32:1815-19.
PURPOSE: Exercise-induced asthma (EIA) occurs in approximately 90% of persons with asthma. The mechanism has not been delineated. Epidemiological studies have suggested that dietary salt may play a role in airway responsiveness. Therefore, the purpose of this study was to determine the influence of both elevated and restricted salt diets on pulmonary function in subjects with EIA.
METHODS: Eight subjects with EIA and eight subjects without EIA (control) participated in a double-blind crossover study. Pulmonary function was determined pre- and post-exercise challenge before and after 2 wk on a normal salt, sodium chloride, diet (NSD), a low salt diet (LSD), and a high salt diet (HSD). A 1-wk washout occurred between diets.
RESULTS: Diet had no effect on preexercise pulmonary function values in either group and had no effect on postexercise pulmonary function values in control subjects. However, LSD improved and HSD worsened postexercise pulmonary function values in EIA subjects. Forced expiratory volume in 1 s (FEV1) decreased by at least 10% in EIA subjects with exercise. In EIA subjects, FEV1 decreased by 14+/-6% on LSD, 20+/-7% on NSD, and 24+/-6% on HSD at 15 min postexercise. Similar patterns were observed for forced vital capacity and peak expiratory flow rates. Although LSD did not normalize pulmonary function in EIA, it did improve it.
CONCLUSIONS: These data suggest that individuals with EIA might benefit from lower salt diets.
Ho R, Cordain L. Biotin insufficiency and cardiovascular disease. Nutrition Research, 2000; 20:1201-12.
Abstract: Among the many contributors to the development of cardiovascular disease are inadequate levels of essential fatty acids. Although the prevalence of essential fatty acid deficiencies (EFAD) have rarely been regarded as problematic in developed nations, studies have shown that insufficient levels of essential fatty acids (EFA) can impact the etiology of cardiovascular disease. Numerous animal studies have shown that clinical symptoms resulting from biotin deficiency are similar to that of EFAD. Many of these studies have also shown low biotin bioavailability in cereal grains. Because the USDA Food Guide Pyramid encourages high carbohydrate intakes and lower consumptions of fat, oil, and protein, not only may EFA level be compromised, but adequate absorption of biotin could be overestimated as well. While static biotin measurements have led many to believe that nutritional status is adequate, functional biotin status may be accommodated. Due to the coenzymatic activity of biotin in the holocarboxylase complexes, insufficient amounts of exogenous biotin could affect elongation and desaturation of EFA, contributing to endothelial cell dysfunction. The authors suggest that there may be a substantial link between cereal grain intakes and cardiovascular disease stemming from both biotin and EFA insufficiencies.
Mickleborough TD, Cordain L, Gotshall RW, Tucker A. A low sodium diet improves indices of pulmonary function in exercise-induced asthma. Journal of Exercise Physiology Online 2000;3(2): http://www.css.edu/users/tboone2/asep/April2000.html
Abstract: The purpose of this study was to determine if manipulation of dietary sodium could influence the severity of exercise-induced asthma (EIA). Fifteen clinically-diagnosed EIA subjects participated in a double-blind, crossover trial. Subjects entered the study on a normal salt diet (NSD), and then were placed either on a low salt diet (LSD) or high salt diet (HSD) for two weeks. Each diet was randomized with a 1-wk washout between diets before crossing over to the alternative diet. Subjects performed a treadmill test to 90% of age-predicted maximum heart rate, which was held for 5 min. Pre- and post-exercise pulmonary function tests were performed following each treatment period. 24-hr urinary sodium excretions were different (p<0.05) for all three diet periods (NSD = 3630 mg/day, LSD = 958 mg/day, HSD = 8133 mg/day). Contrasting pre- to post-exercise changes in pulmonary function measurements, all forced expiratory volumes and flows improved on the LSD; FVC (+0.95 liters), FEV1.0 (+0.4 liters) and FEF25-75% (+0.83 liters/sec). The HSD induced reductions in FVC (-0.22 liters), FEV1.0 (-0.37 liters) and FEF25-75% (-0.55 liters/sec). In conclusion, a HSD caused an increase in severity of EIA, whereas, a LSD represents a potential beneficial therapy for EIA subjects.
Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. British Journal of Nutrition, 2000, 83:207-217.
Abstract: Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T- lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a diminution of disease symptoms in certain patients with RA.
Cordain L, Brand Miller J, Eaton SB, Mann N, Holt SHA, Speth JD. Plant to animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. American Journal of Clinical Nutrition, 2000, 71:682-92.
Abstract: Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45–65 % of energy) of animal food. Most (73 %) of the worldwide hunter-gatherer societies derived > 50 % (≥56-65 % of energy) of their subsistence from animal foods, whereas only 14 % of these societies derived >50 % (≥56-65 % of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19-35 % of energy) at the expense of carbohydrates (22-40 % of energy).
Cordain L, Miller J, Mann N. (1999). Scant evidence of periodic starvation among hunter-gatherers (letter). Diabetologia, 42: 383-84.
Cordain L, (1999). Cereal grains: humanity’s double edged sword. World Review of Nutrition and Dietetics, 84: 19-73.
Eaton SB, Eaton SB Jr, Cordain L, Mann N, Sinclair A. (1998). Dietary intake of long chain polyunsaturated fatty acids during the paleolithic. World Review of Nutrition and Dietetics, 83: 12-23.
Cordain L, (1998). Atherogenic potential of peanut oil based MUFA diets (letter). Lipids, 33: 229-30.
Cordain, L., Gotshall, R.W. and Eaton, S.B. (1998). Physical activity, energy expenditure and fitness: an evolutionary perspective. International Journal of Sports Medicine, 19(5): 328-335.
Abstract: Similar to all other organisms, human structure and function (and consequently our exercise potentials and needs) are genetically determined and were shaped over eons of evolutionary experience by selective pressures of the environmental niche in which our species evolved. Since the emergence of our genus (Homo) more than 2 million years ago until the agricultural revolution of 10,000 years ago, humans have occupied a hunter-gatherer niche. Because the portion of our genetic constitutions which determine fundamental anatomy and physiology have remained relatively unchanged over the past 40,000 years, the exercise capacities and needs of modern humans remain similar to those which had been originally selected by evolution for stone age men and women living as hunter/gatherers. The sedentary nature of contemporary humans living in industrialized societies is vastly at odds with the activity levels required of our ancestors. Present day guidelines for minimal physical activity levels fall 65 % below those observed among living hunter-gatherers. This discordance between our genetically determined exercise requirements and those encountered in present day industrialized societies has been implicated in a wide variety of chronic diseases including obesity, non-insulin dependent diabetes mellitus, coronary heart disease, hypertension and osteoporosis.
Eaton, S.B., Cordain, L. (1997). Old genes, new fuels: Nutritional changes since agriculture. World Review of Nutrition and Dietetics, 81: 26-37.
Cordain, L., Gotshall, R.W., Eaton, S.B. (1997). Evolutionary aspects of exercise. World Review of Nutrition and Dietetics, 81: 49-60.